The involvement of prodynorphin-derived opioid peptides and kappa-opioid receptors in the luteinizing hormone surge on proestrus in the rat

The first study examined whether prodynorphin-derived opioid peptides could block the spontaneous luteinizing hormone (LH) surge and ovulation, and if so, whether through κ-receptors. Dynorphin peptides administered intraventricularly between 1330 and 1800 h in proestrous rats blocked the LH surge and ovulation in a dose-dependent manner, and dynorphin A1–17 and A1–8 were more potent than dynorphin B, α- or β-neoendorphin. The LH surge and ovulation were also blocked by a mixture of five dynorphin peptides, each at a dose that inhibited the surge, and both events were fully restored by coinfusion with the κ-receptor antagonist norbinaltorphimine (nor-BNI). These results demonstrate that dynorphin, acting through κ-receptors, can block the LH surge and ovulation. ^ The second study examined possible involvement of dynorphin and κ-receptors specifically in the medial preoptic area (MPOA) in regulating the LH surge. Push-pull perfusion of the MPOA with antibodies specific for dynorphin A 1–17 or A1–8 from 1030 to 1355 h on proestrus tended to prematurely advance the increase in plasma LH levels normally occurring in the afternoon, suggesting that these two dynorphin peptides might have a role in the MPOA in suppressing LH secretion early on proestrus. MPOA prodynorphin mRNA levels were low at 1700–1800 h on proestrus when plasma LH levels were high, compared with values on the early afternoon of proestrus and diestrus 1. MPOA κ-receptor mRNA levels did not change on proestrus or diestrus 1. These results suggest that a reduction in prodynorphin gene expression on the afternoon of proestrus may be involved in a possible dynorphin disinhibition of LH secretion. ^ The third study examined whether a total loss of κ-opioid inhibition occurs at the onset of the proestrous LH surge. Intraventricular infusion of nor-BNI from 1530 or 1630 to 1850 h on proestrus induced an LH surge that started ½h earlier than the spontaneous surge in controls, and/or attained higher plasma LH levels between 1630 and 1800 h. This advancement and amplification of the LH surge demonstrates that a significant κ-opioid tone is still present during the hours when the LH surge is initiated, and that a complete loss of this tone is not required for the onset of the LH surge on proestrus.